ARTICLES

J Li, I King and AC Sartorelli
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.

The product of the protooncogene c-jun is one of the components of the AP-1
transcription factor complex, which is involved in the control of cell
proliferation and differentiation. To study the role of c-jun in leukemia
cell growth and maturation, a plasmid (pMTJ11) was constructed that
contained the rat c-jun complementary DNA under the control of the human
metallothionein promoter and the neo gene. Murine myelomonocytic WEHI-3B D+
cells were transfected by electroporation with the linearized pMTJ11
plasmid and subsequently cloned in the presence of G-418. Exposure of these
clones to cadmium resulted in a high level of expression of c-jun mRNA and
protein, as demonstrated by Northern hybridization and Western blotting.
When these clones were examined immediately after their establishment,
expression of c-jun was accompanied by the appearance of a mature phenotype
in many clones, as measured by the reduction of nitroblue tetrazolium and
by the expression of Mac-1 (CD11b), a cell surface marker on differentiated
cells. Morphological changes indicative of the differentiated state were
also observed by staining. These findings indicate that expression of c-jun
is capable of initiating the differentiation of WEHI-3B D+ cells in the
absence of an external inducer of maturation. Furthermore, the expression
of c-jun led to an enhancement of the induction of the differentiation of
WEHI-3B D+ cells by retinoic acid, suggesting an involvement of c-jun in
the retinoic acid signal transduction pathway.